Researcher(s)
- Lucy Maxim, Biomedical Engineering, University of Delaware
Faculty Mentor(s)
- Jaclyn Schwarz, Psychological & Brain Sciences, University of Delaware
Abstract
Hypoxic-ischaemic encephalopathy (HIE) is one of the leading causes of neonatal fatalities worldwide. The only current treatment, therapeutic hypothermia (TH), has many limitations. First, it must be performed within 6 hours of birth, and even then, it’s not effective at preventing disabilities and all fatalities. Even with TH, 30% of severe cases still end in fatalities, with male neonates having an increased risk of severe HIE than their female counterparts. Another risk factor for HIE is maternal immune activation (MIA), with nearly 40% of HIE events being associated with MIA. Due to the ineffectiveness of TH for treating severe HIE and its limited availability, there have been many attempts to find an alternative treatment using various animal models and molecules that target immune activation. Among such attempts, amphiregulin has been proposed as an alternative to TH. To better understand the potential impacts of amphiregulin on the neonatal brain, BV2 cell culture experiments were performed.
Our experimental model used two main groups: normoxia and hypoxia. Out of those two groups, half were exposed to lipopolysaccharide (LPS) to stimulate the immune system, simulating MIA. Subsequently, the hypoxia group went through a 6-hour-long hypoxic event approximately 24 hours after LPS exposure. Amphireuglin was administered at varying timepoints for both groups, with some not receiving the drug, some receiving it at the start of the hypoxic event, some receiving it 4 hours into the event, some receiving it 6 hours into the event, and some receiving it 4 hours after the end of the event. These time points aim to explore the anti-inflammatory effects of amphiregulin for the potential treatment of HIE with associated immune activation and to determine the optimal treatment window.